P1057: INDIRECT TREATMENT COMPARISONS OF MOMELOTINIB VS PACRITINIB SAFETY AND ANEMIA OUTCOMES IN PATIENTS WITH MYELOFIBROSIS
Authors: Lucia Masarova, Srdan Verstovsek, Francesca Palandri, Ruben Mesa, Claire Harrison, Balazs Dobi, Boris Gorsh, Zhaohui Wang, Catherine Ellis, Dwaipayan Patnaik, Venediktos Kapetanakis
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: JAK inhibitors (JAKi) are effective in the management of symptoms and splenomegaly in patients (pts) with myelofibrosis (MF) but have varying safety profiles and may be associated with hematologic adverse events (AEs) such as thrombocytopenia and anemia. The JAK1/JAK2/ACVR1 inhibitor momelotinib (MMB) has shown consistent anemia benefits as well as symptom and spleen improvements when evaluated in 3 phase 3 trials. Understanding differences in safety, tolerability, and anemia outcomes between MMB and pacritinib (PAC) can help inform treatment choices in MF. Aims: This study compared safety and anemia outcomes of MMB vs PAC via matching-adjusted indirect comparison (MAIC) of 3 MMB trials (phase 3) and 2 PAC trials (phase 2/3). Methods: Treatment-emergent AEs occurring through 24 weeks in ≥15% of the MMB arm of SIMPLIFY-1 (S1)/SIMPLIFY-2 (S2)/MOMENTUM or the 200-mg twice-daily PAC arm of PERSIST-2/PAC203 were analyzed. Hemoglobin (Hb) improvement at week 24 (in pts with baseline [BL] Hb <10 g/dL) was also assessed; sensitivity analyses with and without inclusion of Hb levels in the 4-week post-transfusion period were performed, as it was unclear how this was handled in PERSIST-2. The analysis population included JAKi-naive and -experienced patients, as PERSIST-2 enrolled both populations and separate data were not reported. Pooled S1/S2/MOMENTUM data were compared vs pooled PERSIST-2/PAC203 data or vs PERSIST-2 data alone, as not all outcomes of interest were reported in PAC203. Evaluable outcomes were limited by published aggregate data, so not all were feasible to compare. MMB pt data were reweighted to match MMB and PAC populations on BL characteristics prioritized by expert clinical input (Figure footnote). Odds ratios (ORs), risk ratios, and risk differences (RDs) vs PAC were evaluated in the balanced populations, matching outcome definitions across trials. MAIC models using different matching characteristics were selected based on effective sample sizes (ESS), distribution of matching weights, and balance of BL characteristics. Sensitivity analyses with alternative models were also performed. Despite adjusting for prognostic factors/effect modifiers, MAIC analyses may be subject to unmeasured/residual confounding. Results: In the base case models, ESS were 80.13 and 97.43 pts when comparing AEs vs PERSIST-2 and PERSIST-2/PAC203, respectively, and 47.64 pts when comparing Hb outcomes vs PERSIST-2. MMB had numerically favorable results for most safety outcomes, with statistically significantly lower odds and risk for all grades of diarrhea, nausea, peripheral edema, and vomiting as well as grade 3/4 and serious AEs (Figure). ORs and RDs for anemia and thrombocytopenia (grade 3/4 or any grade) favored MMB vs PAC, significantly so for grade 3/4 events. No identified safety outcomes were significantly less likely with PAC. MMB was also associated with greater odds/possibility of Hb improvement (both ≥1 g/dL, ≥2 g/dL) regardless of whether post-transfusion Hb levels were excluded (Figure; ≥1 g/dL significant) or included (OR, 30.6 and 8.1; RD, 0.69 and 0.36 for Hb improvement ≥1 g/dL and ≥2 g/dL, respectively; both significant). Sensitivity analysis adjusting for different matching characteristics showed consistency in results for point estimates. Summary/Conclusion: These results suggest MMB provides a more favorable safety profile with fewer grade 3/4 and serious AEs, as well as fewer gastrointestinal and hematologic AEs, including anemia and thrombocytopenia, and a higher chance for Hb improvement vs PAC. FigureKeywords: Anemia, Myelofibrosis